A cohort-based study of host gene expression: tumor suppressor and innate immune/inflammatory pathways associated with the HIV reservoir size.

The major barrier to an HIV cure is the HIV reservoir: latently-infected cells that persist despite effective antiretroviral therapy (ART). There have been few cohort-based studies evaluating host genomic or transcriptomic predictors of the HIV reservoir. We performed host RNA sequencing and HIV reservoir quantification (total DNA [tDNA], unspliced RNA [usRNA], intact DNA) from peripheral CD4+ T cells from 191 ART-suppressed people with HIV (PWH). After adjusting for nadir CD4+ count, timing of ART initiation, and genetic ancestry, we identified two host genes for which higher expression was significantly associated with smaller total DNA viral reservoir size, P3H3 and NBL1, both known tumor suppressor genes. We then identified 17 host genes for which lower expression was associated with higher residual transcription (HIV usRNA). These included novel associations with membrane channel (KCNJ2, GJB2), inflammasome (IL1A, CSF3, TNFAIP5, TNFAIP6, TNFAIP9, CXCL3, CXCL10), and innate immunity (TLR7) genes (FDR-adjusted q<0.05). Gene set enrichment analyses further identified significant associations of HIV usRNA with TLR4/microbial translocation (q = 0.006), IL-1/NRLP3 inflammasome (q = 0.008), and IL-10 (q = 0.037) signaling. Protein validation assays using ELISA and multiplex cytokine assays supported these observed inverse host gene correlations, with P3H3, IL-10, and TNF-α protein associations achieving statistical significance (p<0.05). Plasma IL-10 was also significantly inversely associated with HIV DNA (p = 0.016). HIV intact DNA was not associated with differential host gene expression, although this may have been due to a large number of undetectable values in our study. To our knowledge, this is the largest host transcriptomic study of the HIV reservoir. Our findings suggest that host gene expression may vary in response to the transcriptionally active reservoir and that changes in cellular proliferation genes may influence the size of the HIV reservoir. These findings add important data to the limited host genetic HIV reservoir studies to date.

Combined Gap-Polymerase Chain Reaction and Targeted Next-Generation Sequencing Improve α- and ß-Thalassemia Carrier Screening in Pregnant Women in Vietnam.

Vietnam has a high thalassemia burden. We collected blood samples from 5880 pregnant Vietnamese women during prenatal health checks to assess thalassemia carrier frequency using combined gap-polymerase chain reaction (gap-PCR) and targeted next-generation sequencing (NGS). Thalassemia carriers were identified with prevalence of 13.13% (772), including 7.82% (460) carriers of α-thalassemia (α-thal), 5.31% (312) carriers of ß-thalassemia (ß-thal), and 0.63% (37) concurrent α-/ß-thal carriers. Deletional mutations (368) accounted for 80.0% of α-thal carriers, of which, --SEA (Southeast Asian) (n = 254; 55.0%) was most prevalent, followed by the -α3.7 (rightward) (n = 66; 14.0%) and -α4.2 (leftward) (n = 45; 9.8%) deletions. Hb Westmead (HBA2: c.369C>G) (n = 53) and Hb Constant Spring (Hb CS or HBA2: c.427T>C) (in 28) are the two most common nondeletional α-globin variants, accounting for 11.5 and 6.0% of α-thal carriers. We detected 11 different ß-thal genotypes. Hb E (HBB: c.79G>A) (in 211) accounted for 67.6% of ß-thal carriers. The most common ß-thal genotypes were associated with mutations at codon 17 (A>T) (HBB: c.52A>T), codons 41/42 (-TTCT) (HBB: c.126_129delCTTT), and codon 71/72 (+A) (HBB: c.217_218insA) (prevalence 0.70%, 0.68%, and 0.2%, respectively). Based on mutation frequencies calculated in this study, estimates of 5021 babies in Vietnam are affected with clinically severe thalassemia annually. Our data suggest a higher thalassemia carrier frequency in Vietnam than previously reported. We established that combining NGS with gap-PCR creates an effective large-scale thalassemia screening method that can detect a broad range of mutations.

On the Importance of Secondary Component Properties for Cold Spray Metallization of Carbon Fiber Reinforced Polymers.

In previous studies at McGill University, tin was successfully cold sprayed onto carbon fiber reinforced polymers (CFRPs). A "crack-filling" mechanism was described as the deposition mechanism that allowed deposition of tin onto the CFRP. Improving the coating conductivity for lightning strike protection (LSP) purposes was explored by adding other metal powders (aluminum, copper, zinc) to tin and cold spraying on the CFRP. At the same time, it was noticed that the addition of this secondary component (SC) provided an increase in deposition efficiency (DE); tamping was initially hypothesized to explain this improvement, thus prompting a study solely on the effect of SC hardness. However, it is recognized that other powder characteristics may also be influencing the DE. Thus, in this study, SCs with a wider variety of particle sizes, morphologies, densities and hardness values were mixed with tin and sprayed on CFRPs. The effect of SC properties on tin deposition is discussed and, while SC particle size, morphology and density individually do not notably influence the DE, the impact energy of the SC does. This opens a discussion on optimal parameters for deposition of metals on CFRP, based on results and observations from the literature.

Combined haploidentical and cord blood transplantation for refractory severe aplastic anaemia and hypoplastic myelodysplastic syndrome.

Umbilical cord blood (UCB) transplantation is a potentially curative treatment for patients with refractory severe aplastic anaemia (SAA), but has historically been associated with delayed engraftment and high graft failure and mortality rates. We conducted a prospective phase 2 trial to assess outcome of an allogeneic transplant regimen that co-infused a single UCB unit with CD34+ -selected cells from a haploidentical relative. Among 29 SAA patients [including 10 evolved to myelodysplastic syndrome (MDS)] who underwent the haplo cord transplantation (median age 20 years), 97% had neutrophil recovery (median 10 days), and 93% had platelet recovery (median 32 days). Early myeloid engraftment was from the haplo donor and was gradually replaced by durable engraftment from UCB in most patients. The cumulative incidences of grade II-IV acute and chronic graft-versus-host disease (GVHD) were 21% and 41%, respectively. With a median follow-up of 7·5 years, overall survival was 83% and GVHD/relapse-free survival was 69%. Patient- and transplant-related factors had no impact on engraftment and survival although transplants with haplo-versus-cord killer-cell immunoglobulin-like receptor (KIR) ligand incompatibility had delayed cord engraftment. Our study shows haplo cord transplantation is associated with excellent engraftment and long-term outcome, providing an alternative option for patients with refractory SAA and hypoplastic MDS who lack human leucocyte antigen (HLA)-matched donors.

Cytotoxic components from the leaves of Erythrophleum fordii induce human acute leukemia cell apoptosis through caspase 3 activation and PARP cleavage.

Cassaine diterpenoids as erythrofordins A-C (1-3), pseudo-erythrosuamin (4), and erythrofordin U (5) isolated from the leaves of Vietnamese Erythrophleum fordii Oliver were tested cytotoxic activity against human leukemia cancer cells. The results showed that these metabolites exhibited dose-dependent cytotoxicity against human leukemia HL-60 and KG cells with IC50 values ranging from 15.2 ± 1.5 to 42.2 ± 3.6 µM. Treatment with erythrofordin B led to the apoptosis of HL-60 and KG cells due to the activation of caspase 3, caspase 9, and poly (ADP-ribose) polymerase (PARP). Erythrofordin B significantly increased Bak protein expression, but downregulated the anti-apoptotic protein Bcl-2, in HL-60 cells. In silico results demonstrated that erythrofordin B can bind to both the procaspase-3 allosteric site and the PARP-1 active site, with binding energies of -7.36 and -10.76 kcal/mol, respectively. These results indicated that the leaves of Vietnamese E. fordii, which contain cassaine diterpenoids, can induce the apoptosis of human leukemia cancer cells.

The effects of puberty on associations between mood/personality factors and disordered eating symptoms in girls.

OBJECTIVE: Negative and positive urgency, anxiety, and depressive symptoms are significant factors of disordered eating (DE) symptoms in early adolescence through young adulthood. However, it is unclear how puberty-a critical developmental milestone that is associated with increased risk for DE symptoms-affects the relationship between these factors and DE symptoms, given that the role of pubertal status has rarely been considered in relation to these associations. Thus, the present study examined whether puberty moderates associations between mood/personality factors and DE in pre-adolescent and adolescent girls. METHOD: Participants included 981 girls (aged 8-16 years) from the Michigan State University Twin Registry. Mood/personality factors, pubertal status, and DE were assessed with self-report questionnaires. RESULTS: Puberty significantly moderated associations between several factors (negative urgency, positive urgency, trait anxiety, depressive symptoms) and the cognitive symptoms of DE (e.g., shape/weight concerns, body dissatisfaction). Associations between mood/personality factors and cognitive DE were stronger in girls with more advanced pubertal status. By contrast, no significant moderation effects were detected for mood/personality-dysregulated eating (e.g., binge eating, emotional eating) associations. DISCUSSION: Findings identify pubertal development as an important moderator of mood/personality-DE symptom associations, especially for cognitive DE symptoms that are known to predict the later onset of clinical pathology.

A pilot trial of complement inhibition using eculizumab to overcome platelet transfusion refractoriness in human leukocyte antigen allo-immunized patients.

Heavily transfused patients frequently develop human leukocyte antigen (HLA) allo-immunization resulting in platelet transfusion refractoriness and a high risk for life-threatening thrombocytopenia. Data suggest complement activation leading to the destruction of platelets bound by HLA allo-antibodies may play a pathophysiologic role in platelet refractoriness. Here we conducted a pilot trial to investigate the use of eculizumab, a monoclonal antibody that binds and inhibits C5 complement, to treat platelet transfusion refractoriness in allo-immunized patients with severe thrombocytopenia. A single eculizumab infusion was administered to 10 eligible patients, with four (40%) patients overcoming platelet refractories assessed measuring the corrected platelet count increment (CCI) 10-60 min and 18-24 h post transfusion. Responding patients had a reduction in the requirement for subsequent platelet transfusions and had higher post-transfusion platelet increments for 14 days following eculizumab administration. Remarkably, three of the four responders met CCI criteria for response despite receiving HLA-incompatible platelets. Our results suggest that eculizumab has the ability to overcome platelet transfusion refractoriness in patients with broad HLA allo-immunization. This study establishes proof of principle that complement inhibition can treat platelet transfusion refractoriness, laying the foundation for a large multicentre trial to assess the overall efficacy of this approach (ClinicalTrials.gov, identifier: NCT02298933).

Yttrium-90-labeled anti-CD45 antibody followed by a reduced-intensity hematopoietic cell transplantation for patients with relapsed/refractory leukemia or myelodysplasia.

Outcomes of patients with persistent high-risk leukemia or myelodysplasia prior to allogeneic hematopoietic cell transplantation are dismal. We therefore conducted a phase I trial evaluating the use of CD45-targeted radiotherapy preceding hematopoietic cell transplantation with the goal of improving outcomes for this high-risk scenario. Fifteen patients, median age 62 (range 37-76) years, were treated: ten with advanced acute myeloid leukemia, five with high-risk myelodysplastic syndrome. All patients had evidence of disease prior to treatment including nine with marrow blast counts ranging from 7-84% and six with minimal residual disease. Patients received escalating doses of yttrium-90-labeled anti-CD45 antibody followed by fludarabine and 2 Gy total body irradiation prior to human leukocyte antigen-matched, related or unrelated hematopoietic cell transplantation. Although a maximum dose of 30 Gy was delivered to the liver, no dose-limiting toxicity was observed. Therefore, the maximum-tolerated dose could not be estimated. Treatment led to complete remission in 13 patients (87%). All patients engrafted by day 28. Six patients relapsed, median of 59 (range 6-351) days, after transplantation. The 1-year estimate of relapse was 41%. Eight patients (53%) are surviving with median follow up of 1.8 (range 0.9-5.9) years. Estimated overall survival at one and two years was 66% and 46%, respectively, with progression-free survival estimated to be 46% at each time point. In conclusion, the combination of 90Y-DOTA-BC8 with an allogeneic hematopoietic cell transplantation regimen was feasible and tolerable. This approach appears promising in this high-risk leukemia/myelodysplasia patient population with active disease. (Trial registered at clinicaltrials.gov identifier: NCT01300572).

A semi-GCMC simulation study of electrolytic capacitors with adsorbed titrating peptides.

We use semi-grand canonical Monte Carlo simulations to study an electrolytic capacitor with an adsorbed peptide on the electrode surfaces. Only homogeneous peptides are considered, consisting of only a single residue type. We find that the classical double-hump camel-shaped differential capacitance in such systems is augmented by the addition of a third peak, due to the capacitance contribution of the peptide, essentially superimposed on the salt contribution. This mechanistic picture is justified using a simple mean-field analysis. We find that the position of this third peak can be tuned to various surface potential values by adjusting the ambient pH of the electrolyte solution. We investigate the effect of changing the residue type and the concentration of the adsorbed peptide and of the supporting electrolyte. Varying the residue species and pH allows one to modify the capacitance profile as a function of surface potential, facilitating the design of varying discharging patterns for the capacitor.

Cassaine Diterpenoid Amide from Stem Bark of Erythrophleum fordii Suppresses Cytotoxic and Induces Apoptosis of Human Leukemia Cells.

Cassaine diterpenoids amides from the stem bark of Vietnamese Erythrophleum fordii Oliver were screened for their cytotoxic activity against human cancer cells. The cell proliferation assay results showed that, among the active compounds, 3ß-acetyl-nor-erythrophlamide (3AEP) exhibited the most potential cytotoxicity against human leukemia HL-60 and KG cells with IC50 values of 12.0 ± 1.2 and 18.1 ± 2.7 µM, respectively. Treatment of 3AEP resulted in the apoptosis of HL-60 cells via the activation of caspase 3, and poly (ADP-ribose) polymerase (PARP). Molecular docking in silico results showed that the 3AEP can bind to both the procaspase-3 allosteric site and the PARP-1 active site, with binding energies of -7.51 and -9.63 kcal/mol respectively. These results indicated that the stem bark of Vietnamese E. fordii and its cassaine diterpenoid amides may be useful in the apoptosis induction of human leukemia cancer cells.

Convergence in maternal and child reports of impulsivity, depressive symptoms, and trait anxiety, and their predictive utility for binge-eating behaviors.

OBJECTIVE: Early detection of binge-eating (BE) behaviors and their risk factors is associated with better outcomes. A multi-informant approach for assessing BE psychopathology and risk factors has been emphasized to increase the probability and accuracy of early detection. Impulsivity (particularly negative and positive urgency), trait anxiety, and depressive symptoms are associated with BE behaviors. The present study examined maternal-child convergence of reports of child BE, impulsivity, trait anxiety, and depressive symptoms and examined the predictive power of maternal reports for child-reported BE behaviors. METHOD: Participants included 927 female twins (aged 8-16 years) and 468 mothers from the Michigan State University Twin Registry. Risk factors and BE were assessed with self-report questionnaires. RESULTS: Intraclass correlation coefficients showed fair-to-moderate inter-rater agreement (ICCs = .31-.41) between maternal and child reports of risk factors and low-to-fair agreement for BE (ICCs = .05-.29). Controlling for the effects of age, pubertal status, body mass index, and family relatedness, multilevel models showed that maternal reports of child impulsivity, anxiety, and depressive symptoms did not add predictive power above and beyond child reports. DISCUSSION: Results call into question the utility and practical implications of using maternal reports to supplement child reports for BE and its risk factors.

Vitamin D Status at the Time of Hospitalization for Bronchiolitis and Its Association with Disease Severity.

OBJECTIVE: To investigate the association between circulating 25-hydroxyvitamin D [25(OH)D] status at admission and disease severity among infants hospitalized for bronchiolitis and to determine whether the association differs by the form of 25(OH)D-total, bioavailable or free 25(OH)D. STUDY DESIGN: We conducted a 17-center prospective cohort study of 1016 US infants <12 months old hospitalized with bronchiolitis. Vitamin D status was defined by total 25(OH)D levels, and by calculated levels of bioavailable and free 25(OH)D. Bronchiolitis severity was defined by requirement for intensive care and hospital length-of-stay (LOS). Logistic and Poisson regression were used for unadjusted and multivariable analyses. RESULTS: The median age of hospitalized infants was 3.2 months (IQR 1.6-6.0). The median total 25(OH)D was 26.5 ng/mL (IQR 18.0-33.1); 298 (29%) infants had total 25(OH)D <20 ng/mL. In multivariable models, infants with total 25(OH)D <20 ng/mL had higher risk of requiring intensive care (aOR 1.72, 95% CI 1.12-2.64) and longer LOS (adjusted rate ratio 1.39, 95% CI 1.17-1.65) compared with infants with total 25(OH)D ≥30 ng/mL. Infants with the lowest tertile of bioavailable 25(OH)D, compared with those with the highest tertile, had longer LOS (adjusted rate ratio 1.32, 95% CI 1.07-1.62); admission to the intensive care unit was not statistically significant in the adjusted model (aOR 1.39, 95% CI 0.96-2.64). Free 25(OH)D level was not associated with severity of bronchiolitis in either unadjusted or adjusted models. CONCLUSION: In a large, multicenter cohort of US infants hospitalized for bronchiolitis, infants with total 25(OH)D <20 ng/mL had increased risk of intensive care and longer hospital LOS.

Changes in emergency department concordance with guidelines for the management of stinging insect-induced anaphylaxis: 1999-2001 vs 2013-2015.

BACKGROUND: Changes in emergency department (ED) concordance with guidelines for the management of stinging insect-induced anaphylaxis (SIIA) are not known. OBJECTIVE: To describe temporal changes in ED concordance with guidelines for the management of SIIAs. METHODS: We analyzed data from 2 multicenter retrospective studies of patients with stinging insect-related acute allergic reactions seen in 1 of 14 North American EDs during 2 periods: 1999 through 2001 and 2013 through 2015. Visits were identified similarly across studies (eg, using International Classification of Diseases, Ninth Revision, Clinical Modification codes 989.5, 995.0, and 995.3). Anaphylaxis was defined as an acute allergic reaction with involvement of at least 2 organ systems or hypotension. We compared concordance between periods with 4 guideline recommendations: (1) treatment with epinephrine, (2) discharge prescription for epinephrine auto-injector, (3) referral to an allergist/immunologist, and (4) instructions to avoid the offending allergen. RESULTS: We compared 182 patients with SIIA during 1999 to 2001 with 204 during 2013 to 2015. Any treatment with epinephrine (before arrival to the ED or in the ED) increased over time (30% vs 49%; P < .001). Prescriptions for epinephrine auto-injector at discharge increased significantly (34% vs 57%; P < .001), whereas documentation of referral to an allergist/immunologist decreased (28% vs 12%; P = .002), and instructions to avoid the offending allergen did not change (23% vs 24%; P = .94). Receipt of at least 3 guideline recommendations increased over time; however, the comparison was not statistically significant (10% vs 16%; P = .15). CONCLUSION: During the nearly 15-year study interval, we observed increased ED concordance with epinephrine-related guideline recommendations for the management of SIIA. Reasons for the decrease in allergy/immunology referrals merit further study.

Allogeneic transplantation using CD34+ selected peripheral blood progenitor cells combined with non-mobilized donor T cells for refractory severe aplastic anaemia.

Allogeneic haematopoietic stem cell transplantation is curative for severe aplastic anaemia (SAA) unresponsive to immunosuppressive therapy. To reduce chronic graft-versus-host disease (GVHD), which occurs more frequently after peripheral blood stem cell (PBSC) transplantation compared to bone-marrow transplantation (BMT), and to prevent graft rejection, we developed a novel partial T-cell depleted transplant that infuses high numbers of granulocyte colony-stimulating factor-mobilized CD34+ selected PBSCs combined with a BMT-equivalent dose of non-mobilized donor T-cells. Fifteen patients with refractory SAA received cyclophosphamide, anti-thymocyte globulin and fludarabine conditioning, and were transplanted with a median 8 × 106 CD34+  cells/kg and 2 × 107 non-mobilized CD3+ T-cells/kg from human leucocyte antigen-matched sibling donors. All achieved sustained engraftment with only two developing acute and two developing chronic GVHD. With a 3·5-year median follow-up, 86% of patients survived and were transfusion-independent. When compared to a retrospective cohort of 56 bone-marrow failure patients that received the identical transplant preparative regimen and GVHD prophylaxis with the exception that the allograft contained unmanipulated PBSCs, partial T-cell depleted transplant recipients had delayed donor T-cell chimerism and relative reduction of 75% in the incidence of acute grade II-IV GVHD (13% vs. 52%; P = 0·010) and of 82% in chronic GVHD (13% vs. 72%; P = 0·0004). In multivariate analysis, partial T-cell depleted transplants remained significantly associated with a reduced risk of GVHD. In conclusion, for patients with refractory SAA, this novel transplant strategy achieves excellent engraftment and survival when compared to unmanipulated PBSC transplants and dramatically reduces the incidence of both acute and chronic GVHD.

Individual factors, neighborhood social context and asthma at age 5 years.

OBJECTIVE: Childhood asthma is a major public health problem and its development is multifactorial. We examined whether neighborhood cohesion and disorder were associated with caregiver-report of asthma at age 5 years. METHODS: This study is a secondary data analysis of the 2011-2012 United States National Survey of Children's Health. Data were available for 4680 children, age 5 years old born at term or preterm with birthweight >2500 g. Neighborhood disorder and cohesion were assessed based on caregivers' responses to validated questionnaires. Child asthma diagnosis was reported by the caregiver. Multivariable logistic regression was used to examine the relationship between these neighborhood factors and caregiver-report of child asthma, while accounting for individual level covariates. RESULTS: Approximately two-thirds of the 4680 children were White and lived in households with income >400% of federal poverty line. Asthma was present in 399 (9%) children. Child female sex was associated with reduced risk of caregiver-reported asthma while non-Hispanic Black race and having smokers in the household were independently associated with increased risk in multivariable models. In these models, neighborhood disorder was significantly associated with asthma (adjusted Odds Ratio [aOR] 1.70, 95% Confidence Interval [CI] 1.04-2.78), while neighborhood cohesion was not (aOR 0.93, 95% CI 0.51-1.68). CONCLUSION: Even after adjustment for several individual level factors, neighborhood disorder was associated with caregiver-report of asthma in this nationally representative sample of 5-year-old children. Further research is needed to better understand how risk factors at different levels of the socio-ecological framework may interact to affect childhood asthma development.

Physicians' adherence to acute coronary syndrome prescribing guidelines in Vietnamese hospital practice: a cross-sectional study.

OBJECTIVES: To determine the extent of physicians' adherence to prescribing guidelines for acute coronary syndrome in Vietnamese hospitals. METHODS: Retrospective cross-sectional study of medical records of all patients with ACS admitted to two public hospitals in Ho Chi Minh City, Vietnam, from January to December 2013. Percentages of eligible patients receiving guideline-recommended medications were determined. Factors associated with non-adherence were identified using multivariate logistic regression. RESULTS: Overall, 711 medical records were reviewed and 284 patients fulfilled inclusion criteria (mean age 64 years; 69.4% male). Of those patients eligible for treatment, aspirin was prescribed for 97.9% at arrival and 96.3% at discharge; dual antiplatelet therapy was prescribed for 92.3% at arrival and 91.7% at discharge; loading doses were prescribed for 79.5% (aspirin) and 55.8% (clopidogrel); beta blockers were prescribed for 58.7% at arrival and 76.7% at discharge; angiotensin-converting enzyme inhibitors or angiotensin receptor blockers (ACEI/ARB) were prescribed for 89.1% at arrival or discharge; and statins were prescribed for 94.1% at arrival and 90.7% at discharge. Patients undergoing an invasive procedure were more likely to receive guideline-recommended medications at discharge: dual antiplatelet therapy (OR 3.77; 95% CI 1.23-11.52), beta blocker (OR 3.95; 95% CI 1.86-8.40) and ACEI/ARB (OR 4.01; 95% CI 1.30-12.41). Ninety of the excluded patients were discharged without completing treatment. CONCLUSIONS: In general, physicians closely adhered to ACS prescribing guidelines in Vietnamese hospital practice. Prescribing of beta blockers and clopidogrel loading doses was probably suboptimal. Why patients do not complete treatment needs to be investigated.

Respiratory failure.

On the basis of research evidence, (1)(2) numerous diseases and conditions can impair gas exchange, resulting in failure to meet the body's metabolic demands and leading to respiratory failure. On the basis of consensus, (1)(2)(7)(8)(9)(10) the clinical presentations of respiratory failure depend on the underlying cause and the level of hypoxemia and hypercapnia. Early diagnosis, close monitoring, and timely intervention are of utmost importance. On the basis of research evidence, (5)(14)(25) interventions range from noninvasive methods, such as close monitoring and supplemental oxygen, to full respiratory support with mechanical ventilation and in extreme cases even the use of extracorporeal membrane oxygenation.

Sporadic Pemphigus Foliaceus in a 3-Year-Old Vietnamese Girl: A Case Report and Literature Review.

Pemphigus foliaceus is an uncommon autoimmune intraepidermal blistering disease characterized by immunoglobulin (Ig) G autoantibodies that attack desmoglein-1 in the epidermis. There are two predominant forms of pemphigus foliaceus, sporadic and endemic. Sporadic pemphigus foliaceus is known to be more prevalent in middle-aged and elderly people and to be extremely rare in children. Less than 40 nonendemic pediatric pemphigus foliaceus cases have been documented in the literature. This report documents a case of sporadic pemphigus foliaceus in a 3-year-old Vietnamese girl who presented with generalized scaling and crusted erosions over the body.

Targeted Radiation Delivery before Haploidentical HCT for High-risk Leukemia or MDS Patients Yields Long-term Survivors.

PURPOSE: Hematopoietic cell transplantation (HCT) has curative potential for myeloid malignancies, though many patients cannot tolerate myeloablative conditioning with high-dose chemotherapy alone or with total-body irradiation (TBI). Here we report long-term outcomes from a phase I/II study using iodine-131 (131I)-anti-CD45 antibody BC8 combined with nonmyeloablative conditioning prior to HLA-haploidentical HCT in adults with high-risk relapsed/ refractory acute myeloid or lymphoid leukemia (AML or ALL), or myelodysplastic syndrome (MDS; ClinicalTrials.gov, NCT00589316). PATIENTS AND METHODS: Patients received a tracer diagnostic dose before a therapeutic infusion of 131I-anti-CD45 to deliver escalating doses (12-26 Gy) to the dose-limiting organ. Patients subsequently received fludarabine, cyclophosphamide (CY), and 2 Gy TBI conditioning before haploidentical marrow HCT. GVHD prophylaxis was posttransplant CY plus tacrolimus and mycophenolate mofetil. RESULTS: Twenty-five patients (20 with AML, 4 ALL and 1 high-risk MDS) were treated; 8 had ≥ 5% blasts by morphology (range 9%-20%), and 7 had previously failed HCT. All 25 patients achieved a morphologic remission 28 days after HCT, with only 2 patients showing minimal residual disease (0.002-1.8%) by flow cytometry. Median time to engraftment was 15 days for neutrophils and 23 days for platelets. Point estimates for overall survival and progression-free survival were 40% and 32% at 1 year, and 24% at 2 years, respectively. Point estimates of relapse and nonrelapse mortality at 1 year were 56% and 12%, respectively. CONCLUSIONS: 131I-anti-CD45 radioimmunotherapy prior to haploidentical HCT is feasible and can be curative in some patients, including those with disease, without additional toxicity.

Financial Toxicity, Time Toxicity, and Quality of Life in Multiple Myeloma.

BACKGROUND: Patients with multiple myeloma (MM) may be on therapy for years, which can lead to financial toxicity (FinTox) or time toxicity (TimeTox). The prevalence, predictors, and quality of life (QOL) impacts of FinTox and TimeTox during different phases of MM treatment have not been characterized. PATIENTS AND METHODS: We conducted a single-center cross-sectional survey of patients with MM who had undergone transplantation. FinTox+ was defined as a COST-FACIT score <23, TimeTox+ as MM-related interactions (including phone calls) ≥1x weekly or ≥1x monthly in-person among far-residing patients, QOL using PROMIS Global Health, and functional status using patient-reported Karnofsky performance status (KPS). RESULTS: Of 252 patients, 22% and 40% met FinTox+ and TimeTox+ criteria respectively. Respective FinTox+ and TimeTox+ proportions were 22%/37% for patients on maintenance, 22%/82% with active therapy, and 20%/14% with observation. FinTox+ predictors included annual income (P < .01) and out-of-pocket costs (P < .01). TimeTox+ predictors included disease status (P < .001), caregiver status (P = .01), far-residing status (P < .001), and out-of-pocket costs (P = .03). FinTox+ was associated with a clinically meaningful decrease in mental QOL, while TimeTox+ patients were more likely to have KPS ≤ 80. CONCLUSIONS: In our large study, monetary status but not disease status predicted FinTox. Over a third of patients on maintenance reported TimeTox. FinTox+ was associated with decreased mental health, while TimeTox+ was associated with worse performance status. These two toxicities may negatively impact patient wellbeing, and studies of strategies to mitigate their impact are in development.